| Modification Notes |
Cubilin is an endocytic receptor that lacks a classical transmembrane region (1). It is a multidomain receptor that contains an amino terminal 110 residue segment followed by 8 epidermal growth factor (EGF)-like repeats and a contiguous stretch of 27 CUB domains (2). The gene encoding human cubulin maps to chromosome 10 and it is predominantly expressed in intestine, kidney and yolk sac (1–3). It also is expressed in intestinal membranes (2). Cubilin colocalizes with and binds to megalin, a member of the LDL receptor family that is required for the internalization of cubulin-bound ligands, such as vitamin B12, apolipoprotein A1 and albumin (1,2,4,5). Megalin specifically binds to cubilin in the amino terminal region that contains the EGF-like repeats and CUB domains 1 and 2 (2). Mutations in the cubulin gene are thought to cause megaloblastic anemia 1 (MGA1), an autosomal recessive disorder also known as Imerslund-Grasbeck’s disease, which causes intestinal malabsorption of vitamin B12 (3,6,7). |
